WO1997032880A1 - PYRIMIDO[5,4-d]PYRIMIDINE, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL, DEREN VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG - Google Patents

Info

Publication number

WO1997032880A1

WO1997032880A1 PCT/EP1997/001047 EP9701047W WO9732880A1 WO 1997032880 A1 WO1997032880 A1 WO 1997032880A1 EP 9701047 W EP9701047 W EP 9701047W WO 9732880 A1 WO9732880 A1 WO 9732880A1

Authority

WO

WIPO (PCT)

Prior art keywords

amino

group

pyrimido

methyl

pyrimidine

Prior art date

1996-03-06

Links

• Espacenet
• Global Dossier
• PatentScope
• Discuss

• JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical class N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 title claims abstract description 92
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 13
• 150000001875 compounds Chemical class 0.000 title claims description 123
• 238000000034 method Methods 0.000 title claims description 8
• 239000003814 drug Substances 0.000 title claims description 7
• 230000008569 process Effects 0.000 title claims description 6
• 150000003839 salts Chemical class 0.000 claims abstract description 27
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 7
• 150000007524 organic acids Chemical class 0.000 claims abstract description 5
• 150000007522 mineralic acids Chemical class 0.000 claims abstract description 4
• 235000005985 organic acids Nutrition 0.000 claims abstract description 4
• -1 trifluoromethoxy, methyl Chemical group 0.000 claims description 1025
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 148
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 39
• 125000000217 alkyl group Chemical group 0.000 claims description 30
• 125000003282 alkyl amino group Chemical group 0.000 claims description 27
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 25
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
• 239000000460 chlorine Substances 0.000 claims description 21
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 21
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 21
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 125000003277 amino group Chemical group 0.000 claims description 20
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 20
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 18
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 16
• 230000003647 oxidation Effects 0.000 claims description 16
• 238000007254 oxidation reaction Methods 0.000 claims description 16
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 15
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 14
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 14
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 12
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 12
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 12
• 150000003254 radicals Chemical group 0.000 claims description 12
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 8
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 150000001412 amines Chemical class 0.000 claims description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 239000001301 oxygen Substances 0.000 claims description 8
• 230000035755 proliferation Effects 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 7
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 6
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
• 229910052801 chlorine Inorganic materials 0.000 claims description 6
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 150000002148 esters Chemical class 0.000 claims description 6
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 230000001681 protective effect Effects 0.000 claims description 6
• 125000006413 ring segment Chemical group 0.000 claims description 6
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 5
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• ZDCCULNSINBBDM-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(piperidin-4-ylmethyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCC1CCNCC1 ZDCCULNSINBBDM-UHFFFAOYSA-N 0.000 claims description 4
• UIYDNRPJDAKFEE-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-[(1-methylpiperidin-4-yl)methyl]pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCC1CNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 UIYDNRPJDAKFEE-UHFFFAOYSA-N 0.000 claims description 4
• VYIISGRSCFDALJ-UHFFFAOYSA-N 4-n-(6-morpholin-4-ylpyrimido[5,4-d]pyrimidin-4-yl)-2-nitrobenzene-1,4-diamine Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1NC1=NC=NC2=CN=C(N3CCOCC3)N=C12 VYIISGRSCFDALJ-UHFFFAOYSA-N 0.000 claims description 4
• XBARGVDOISHQKQ-HOMQSWHASA-N C1=C(Br)C(N)=C(Br)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 Chemical compound C1=C(Br)C(N)=C(Br)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 XBARGVDOISHQKQ-HOMQSWHASA-N 0.000 claims description 4
• NJHIXVCSVBZKRX-UMSPYCQHSA-N ClC1=C(C=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)O)[N+](=O)[O-] Chemical compound ClC1=C(C=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)O)[N+](=O)[O-] NJHIXVCSVBZKRX-UMSPYCQHSA-N 0.000 claims description 4
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
• XWJDVVZLQSQCAV-UMSPYCQHSA-N Nc1ccc(Nc2ncnc3cnc(N[C@H]4CC[C@H](O)CC4)nc23)cc1[N+]([O-])=O Chemical compound Nc1ccc(Nc2ncnc3cnc(N[C@H]4CC[C@H](O)CC4)nc23)cc1[N+]([O-])=O XWJDVVZLQSQCAV-UMSPYCQHSA-N 0.000 claims description 4
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
• 150000001408 amides Chemical class 0.000 claims description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
• 230000032050 esterification Effects 0.000 claims description 4
• 238000005886 esterification reaction Methods 0.000 claims description 4
• 229910052731 fluorine Inorganic materials 0.000 claims description 4
• 239000011737 fluorine Substances 0.000 claims description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
• 125000006626 methoxycarbonylamino group Chemical group 0.000 claims description 4
• DTNQTMAGMDRICO-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-[4-(1-methylpiperidin-4-yl)piperidin-1-yl]pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCC1C1CCN(C=2N=C3C(NC=4C=C(Cl)C(F)=CC=4)=NC=NC3=CN=2)CC1 DTNQTMAGMDRICO-UHFFFAOYSA-N 0.000 claims description 4
• 239000000126 substance Substances 0.000 claims description 4
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 4
• 125000004434 sulfur atom Chemical group 0.000 claims description 4
• NDZPCTMEAPKWLH-UHFFFAOYSA-N 1-[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]piperidin-4-ol Chemical compound C1CC(O)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 NDZPCTMEAPKWLH-UHFFFAOYSA-N 0.000 claims description 3
• JBJSTJGOHXNHES-UHFFFAOYSA-N 1-[4-[2-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]ethyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CCNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 JBJSTJGOHXNHES-UHFFFAOYSA-N 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
• DSJNHTGFNMAKQS-UHFFFAOYSA-N 4-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]piperidine-1-carbonitrile Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CCN(C#N)CC1 DSJNHTGFNMAKQS-UHFFFAOYSA-N 0.000 claims description 3
• YCKBKLQNSNOZCC-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(3-morpholin-4-ylpropyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCCCN1CCOCC1 YCKBKLQNSNOZCC-UHFFFAOYSA-N 0.000 claims description 3
• YYHURUCEAOGAFA-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(4-morpholin-4-ylcyclohexyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CCC(N2CCOCC2)CC1 YYHURUCEAOGAFA-UHFFFAOYSA-N 0.000 claims description 3
• JSLIYIRAEYINIM-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(4-pyrrolidin-1-ylcyclohexyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CCC(N2CCCC2)CC1 JSLIYIRAEYINIM-UHFFFAOYSA-N 0.000 claims description 3
• LHMSGUCCOMYASZ-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-piperidin-3-ylpyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CNCCC1 LHMSGUCCOMYASZ-UHFFFAOYSA-N 0.000 claims description 3
• JKWQTABCEDZHMO-UHFFFAOYSA-N 6-(4-amino-4-methylpiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(C)(N)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 JKWQTABCEDZHMO-UHFFFAOYSA-N 0.000 claims description 3
• VORHRQJEKLYXKI-UHFFFAOYSA-N 6-(4-aminoazepan-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(N)CCCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 VORHRQJEKLYXKI-UHFFFAOYSA-N 0.000 claims description 3
• XLGCTOXPKQVOOU-UHFFFAOYSA-N 6-[4-(aminomethyl)piperidin-1-yl]-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(CN)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 XLGCTOXPKQVOOU-UHFFFAOYSA-N 0.000 claims description 3
• LEUJFISHIOATTG-UHFFFAOYSA-N 6-n-(1-azabicyclo[2.2.2]octan-4-ylmethyl)-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCC1(CC2)CCN2CC1 LEUJFISHIOATTG-UHFFFAOYSA-N 0.000 claims description 3
• GJMXSLKSMVMHQM-UHFFFAOYSA-N 6-n-(2-amino-2-methylpropyl)-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C12=NC(NCC(C)(N)C)=NC=C2N=CN=C1NC1=CC=C(F)C(Cl)=C1 GJMXSLKSMVMHQM-UHFFFAOYSA-N 0.000 claims description 3
• KPZKEICOCNZRSE-UHFFFAOYSA-N 6-n-[[3-(aminomethyl)cyclohexyl]methyl]-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1C(CN)CCCC1CNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 KPZKEICOCNZRSE-UHFFFAOYSA-N 0.000 claims description 3
• SHYIUIWRSJPFDA-HZCBDIJESA-N C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)N(C)C Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)N(C)C SHYIUIWRSJPFDA-HZCBDIJESA-N 0.000 claims description 3
• HDBREMCJUIQJGV-HOMQSWHASA-N C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 Chemical compound C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 HDBREMCJUIQJGV-HOMQSWHASA-N 0.000 claims description 3
• KMHLXHOWFPMNMT-UHFFFAOYSA-N [4-[2-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]ethyl]piperazin-1-yl]-morpholin-4-ylmethanone Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCCN1CCN(C(=O)N2CCOCC2)CC1 KMHLXHOWFPMNMT-UHFFFAOYSA-N 0.000 claims description 3
• 125000002252 acyl group Chemical group 0.000 claims description 3
• 230000010933 acylation Effects 0.000 claims description 3
• 238000005917 acylation reaction Methods 0.000 claims description 3
• 230000029936 alkylation Effects 0.000 claims description 3
• 238000005804 alkylation reaction Methods 0.000 claims description 3
• 230000009435 amidation Effects 0.000 claims description 3
• 238000007112 amidation reaction Methods 0.000 claims description 3
• 201000011510 cancer Diseases 0.000 claims description 3
• 150000001728 carbonyl compounds Chemical class 0.000 claims description 3
• 239000000969 carrier Substances 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000004185 ester group Chemical group 0.000 claims description 3
• ZQDZBQSEODKVNP-UHFFFAOYSA-N methyl n-[1-[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 ZQDZBQSEODKVNP-UHFFFAOYSA-N 0.000 claims description 3
• GFKYMYYJOGXQBW-UHFFFAOYSA-N methyl n-[3-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]propyl]carbamate Chemical compound C12=NC(NCCCNC(=O)OC)=NC=C2N=CN=C1NC1=CC=C(F)C(Cl)=C1 GFKYMYYJOGXQBW-UHFFFAOYSA-N 0.000 claims description 3
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 3
• ZJUBWLYEKZUHOB-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(4-morpholin-4-ylpiperidin-1-yl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CN=C(N3CCC(CC3)N3CCOCC3)N=C12 ZJUBWLYEKZUHOB-UHFFFAOYSA-N 0.000 claims description 3
• FPZZRINZZMYKHL-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(4-piperidin-4-ylpiperidin-1-yl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CN=C(N3CCC(CC3)C3CCNCC3)N=C12 FPZZRINZZMYKHL-UHFFFAOYSA-N 0.000 claims description 3
• DNMZGZNLNVVEHS-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(4-pyrrolidin-1-ylpiperidin-1-yl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CN=C(N3CCC(CC3)N3CCCC3)N=C12 DNMZGZNLNVVEHS-UHFFFAOYSA-N 0.000 claims description 3
• OMVYAPIWXONNFV-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(oxan-4-yloxy)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2OC1CCOCC1 OMVYAPIWXONNFV-UHFFFAOYSA-N 0.000 claims description 3
• JGNKOJPHBUJTJZ-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(oxolan-3-yloxy)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2OC1COCC1 JGNKOJPHBUJTJZ-UHFFFAOYSA-N 0.000 claims description 3
• TWPVDIOCVXCQIV-UHFFFAOYSA-N n-[4-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]cyclohexyl]-n-methylacetamide Chemical compound C1CC(N(C)C(C)=O)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 TWPVDIOCVXCQIV-UHFFFAOYSA-N 0.000 claims description 3
• 238000005932 reductive alkylation reaction Methods 0.000 claims description 3
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